Hepatocellular carcinoma (HCC) is reported to afflict as many as 260,000 individuals each year world-wide, making it the eighth most frequent cancer in the world. Cirrhosis has been implicated as a predisposing condition for HCC in a majority of patients who develop HCC in low risk populations. Approximately eighty to ninety percent of HCC cases have been found to occur in patients suffering from cirrhotic liver. See, Lotze, M. T., et al., "Hepatobiliary Neoplasms," in CANCER. Principles and Practice of Oncology, Devita V. T. J. et al., eds., 883-915 (1993); Azzarone, F. A., et al., Eur. J. Cancer Prevention, 1 (Suppl. 3):55-58 (1992).
Current therapies for liver cirrhosis include treatment with corticosteroids and interferon-.alpha.. However, in more severe cases, a liver transplant is often the only recourse. Similarly, treatment for benign and malignant liver tumors is often either a liver resection or a liver transplant. These more drastic treatments are both very risky and very expensive. Thus, early diagnosis and treatment of liver neoplastic diseases, such as liver cirrhosis and HCC, is highly desirable.
It has been reported that .alpha.-fetoprotein and IGF-II are expressed in the liver tissue of approximately 30% of those individuals afflicted with HCC, but not in normal adult liver. Unfortunately, these proteins appear more frequently in late stage HCC and thus, are not suitable for the development of an early diagnostic test.
Efforts to develop methods for diagnosis and treatment have been slowed by the lack of understanding of the pathology of HCC. In spite of the clinical importance of liver cirrhosis and HCC, the mechanism of HCC development still remains obscure. Tremendous gaps exist in the current understanding of basic pathologic mechanisms that lead to the development of HCC. Accordingly, the identification of genetic markers associated with liver neoplastic diseases, such as liver cirrhosis and HCC, for use as a tool in diagnosis and in the further elucidation of the pathology of these diseases, is highly desirable.